The transcription factor ZEB1 (δEF1) represses Plakophilin 3 during human cancer progression
The transcription factor ZEB1 (δEF1) represses Plakophilin 3 during human cancer progression
复制标题
DOI：
10.1016/j.febslet.2007.03.026
复制
发表时间：
2007-04-17
期刊：
影响因子：
3.5
通讯作者：
Eger, Andreas
中科院分区：
文献类型：
--
作者：
Aigner, Kirsten;Descovich, Luise;Eger, Andreas
亲Plakophilin 3 （PKP3）属于p120ctn家族，是犰狳相关蛋白，主要在桥粒形成中起作用。在这里，我们报道了转移癌细胞中PKP3被f -钙粘蛋白抑制因子ZEB1转录抑制。ZEB1物理上与PKP3启动子中的两个保守的E-box元件结合，并在报告基因检测中部分抑制相应的人和小鼠PKP3启动子片段的活性。在人类肿瘤中，侵袭性癌细胞在肿瘤-宿主界面处ZEB1表达上调，同时伴随PKP3表达水平下调。因此，ZEB1对PKP3的转录抑制有助于ZEB1介导的细胞间粘附和上皮向间质转化的瓦解。(c) 2007年欧洲生化学会联合会。Elsevier B.V.版权所有。
Plakophilin 3 (PKP3) belongs to the p120ctn family of armadillo-related proteins predominantly functioning in desmosome formation. Here we report that PKP3 is transcriptionally repressed by the F-cadherin repressor ZEB1 in metastatic cancer cells. ZEB1 physically associates with two conserved E-box elements in the PKP3 promoter and partially represses the activity of corresponding human and mouse PKP3 promoter fragments in reporter gene assays. In human tumours ZEB1 is upregulated in invasive cancer cells at the tumour-host interface, which is accompanied by downregulation of PKP3 expression levels. Hence, the transcriptional repression of PKP3 by ZEB1 contributes to ZEB1-mediated disintegration of intercellular adhesion and epithelial to mesenchymal transition. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.